The role of extracellular matrix in CNS regeneration

Busch, Sarah A.; Silver, Jerry

doi:10.1016/j.conb.2006.09.004

Cited by 422 publications

(320 citation statements)

References 59 publications

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“…Traditionally, thought to be a simple mechanical barrier (Windle and Chambers, 1950), later studies suggested that regeneration still fails even when a dense glial scar does not form (Guth et al, 1986). Multiple models have now demonstrated that the molecular composition of the scar and the production of inhibitory molecules by astrocytes are contributing factors for regenerative failure (Busch and Silver, 2007;Fawcett, 2006;Fitch and Silver, 1997a;Fitch and Silver, 2000;Liu et al, 2006;McGraw et al, 2001;Silver and Miller, 2004;Yiu and He, 2006;Zhang et al, 2006). Reactive astrocytes within the glial scar have been shown to upregulate molecules such as tenascin (Apostolova et al, 2006;Brodkey et al, 1995;McKeon et al, 1995), Semaphorin 3 (Pasterkamp et al, 2001), ephrin-B2 (Bundesen et al, 2003), slit proteins (Hagino et al, 2003), and a host of chondroitin sulfate proteoglycans (Jones et al, 2003a;McKeon, et al, 1995;Rhodes and Fawcett, 2004).…”

Section: Molecules Within the Glial Scar Contribute To Regenerative Fmentioning

confidence: 99%

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

Fitch

Silver

2008

Experimental Neurology

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Spinal cord and brain injuries lead to complex cellular and molecular interactions within the central nervous system in an attempt to repair the initial tissue damage. Many studies have illustrated the importance of the glial cell response to injury, and the influences of inflammation and wound healing processes on the overall morbidity and permanent disability that result. The abortive attempts of neuronal regeneration after spinal cord injury are influenced by inflammatory cell activation, reactive astrogliosis and the production of both growth promoting and inhibitory extracellular molecules. Despite the historical perspective that the glial scar was a mechanical barrier to regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Unlike myelin associated inhibitory molecules, which remain at largely static levels before and after central nervous system trauma, inhibitory extracellular matrix molecules are dramatically upregulated during the inflammatory stages after injury providing a window of opportunity for the delivery of candidate therapeutic interventions. While high dose methylprednisolone steroid therapy alone has not proved to be the solution to this difficult clinical problem, other strategies for modulating inflammation and changing the make up of inhibitory molecules in the extracellular matrix are providing robust evidence that rehabilitation after spinal cord and brain injury has the potential to significantly change the outcome for what was once thought to be permanent disability.

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Section: Molecules Within the Glial Scar Contribute To Regenerative Fmentioning

confidence: 99%

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

Fitch

Silver

2008

Experimental Neurology

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865

657

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“…Different glial reactions were found in the LOTs transected on P7 and P14 with mild astrocytic reaction of the former and its intense reaction of the latter, and astrocytes at the injured site were known to produce axon-inhibitory molecules [4,6,19]. Similar critical periods of axonal regeneration in the corticospinal tract of different developmental stages of rats who received spinal cord injuries on P0, P6, and P12 were reported to be between 6 and 12 postnatal days [2,5].…”

Section: Discussionmentioning

confidence: 96%

Analysis of spontaneous regeneration of olfactory structures with emphasis on myelination and re-innervation of cortical areas

Fukushima¹,

Yokouchi²,

Sakamoto³

et al. 2013

Neuroscience Letters

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Regeneration of the lateral olfactory tract (LOT) occurs spontaneously after transection in developing rats. In neonatally LOT-transected rats, we observed a newly-formed myelinated tract near the rhinal sulcus. The aim of this study was to analyze the precise re-innervated cortical areas and to demonstrate ectopic LOT myelination in neonatally LOT-transected rats. Neonatal rats were subjected to unilateral LOT transection and simultaneous injection of a retrograde fluorescent tracer into the posterior olfactory cortex to evaluate the degree of transection. After 8 weeks, bilateral olfactory bulbs of the rats were subjected to multiple injections of an anterograde neuronal tracer to determine the extent of the regenerated fibers. In the completely LOT-transected rats, the regenerated fibers were distributed in the anterior olfactory cortices; the anterior olfactory nucleus, the olfactory tubercle, and the rostral part of the piriform cortex.Ectopic myelination of LOT was evident immediately below the rhinal sulcus in the completely and incompletely LOT-transected rats. We concluded that the regenerated bulbar fibers were confined to the regions of the anterior olfactory cortices and that ectopic myelination of the regenerated LOT occurred only at a specific site near the rhinal sulcus.

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“…A variety of natural biomaterials mostly present within the extracellular matrix (ECM) provide both structural and growth support to axons during development [13,14] and maturity [15] as well as after injury [16] . Collagen, laminin, fibronectin, vitronectin, and proteoglycans/ glycosaminoglycans [14] are all members of this particular group of materials.…”

Section: Polymersmentioning

confidence: 99%

Biomaterials for spinal cord repair

Haggerty

Oudega

2013

Neurosci. Bull.

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Spinal cord injury (SCi) results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCi is that damaged axons do not regenerate, which prevents the re-establishment of axonal circuits involved in function. Many groups are working to develop treatments that address the lack of axon regeneration after SCi. The emergence of biomaterials for regeneration and increased collaboration between engineers, basic and translational scientists, and clinicians hold promise for the development of effective therapies for SCi. A plethora of biomaterials is available and has been tested in various models of SCi. Considering the clinical relevance of contusion injuries, we primarily focus on polymers that meet the specific criteria for addressing this type of injury. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Designing materials to address the specific needs of the damaged central nervous system is crucial and possible with current technology. Here, we review the most prominent materials, their optimal characteristics, and their potential roles in repairing and regenerating damaged axons following SCi.Keywords: spinal cord injury; axon regeneration; biodegradable materials; extracellular matrix proteins; functional recovery; growth factor; guidance; injury and repair; spinal motor neuron IntroductionSpinal cord injury (SCi) causes loss of neurons and axons resulting in motor and sensory function impairments. There are thousands of new cases of SCi in the world annually [1,2] occurring often in young adults. The lack of endogenous repair and the significant costs to the individual, family and society [1] are important motivations behind the continuing efforts to develop effective therapies. Promoting axonal regeneration is considered a potential repair strategy because it could lead to recovery of axonal circuits involved in motor and/or sensory function [3] .The central nervous system (CNS) neurons are intrinsically capable of some regeneration of damaged axons [4] but their attempts after SCi are frustrated by structural and chemical obstructions in the damaged nervous tissue [5] . Spinal cord repair approaches typically lead to small functional gains. one feature that most of these approaches have in common is a poor axonal regeneration response, suggesting that promoting axonal regeneration, including synapse formation, is essential to achieve substantial functional repair after SCi. if so, it is rational to anticipate that effective spinal cord therapies will need to include interventions addressing the axon growth-inhibition that leads to the poor axonal growth responses. As introduced above, axonal regeneration is considered an important repair mechanism for the injured spinal cord. Therefore, this review focuses on materials that have shown most promise to elicit an axonal regeneration response to foster functional restoration after ...

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The role of extracellular matrix in CNS regeneration

Cited by 422 publications

References 59 publications

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

Analysis of spontaneous regeneration of olfactory structures with emphasis on myelination and re-innervation of cortical areas

Biomaterials for spinal cord repair

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